Neurokinin blockers
Fezolinetant and elinzanetant are non-hormonal pills for hot flashes that work on the part of the brain that sets off each flush. They cut hot flashes by roughly 60–65% in their trials, but placebo did a lot of that too, leaving the drugs about 25 percentage points; fezolinetant also carries a US boxed warning for rare serious liver injury.
Neurokinin blockers are a real option if you can't or won't take hormone therapy, but not a casual one: get liver tests before starting and keep to the follow-up schedule. Fezolinetant needs five follow-up liver tests in the first nine months; elinzanetant needs one.
What they are
Hot flashes start in a group of temperature-control nerve cells in the hypothalamus, at the base of the brain. These cells respond to neurokinins, signalling molecules, through receptors called NK1 and NK3. Fezolinetant blocks NK3; elinzanetant blocks both NK1 and NK3. Neither involves any hormone exposure.
They are aimed at women who need hot-flash relief but should not take menopausal hormone therapy: for example after a hormone-receptor-positive breast cancer, with an active blood clot, unexplained vaginal bleeding, or severe uncontrolled heart disease.
How well they work: real, but smaller than the headline
In their 12-week trials, both drugs cut the frequency of hot flashes by roughly 60–65%. But hot flashes also fell 37–43% in the placebo groups of the same trials, so the drugs' own contribution is roughly 25 percentage points [1][2].
Large placebo responses are common in hot-flash trials. For antidepressants such as paroxetine it swallows most of the effect: across six paroxetine trials in 1,486 women, 79% of the improvement in hot-flash frequency was matched on placebo [3].
The liver: the two drugs are not interchangeable
Fezolinetant has carried a US boxed warning for serious liver injury since December 2024. The label requires liver tests before starting, monthly for the first three months, and again at months 6 and 9, and it must not be started in anyone whose liver enzymes or bilirubin are already at twice the upper limit of normal [4]. The injury is described as rare, but no incidence rate has been published.
Elinzanetant was approved in the US in October 2025 and in the EU a month later. It carries no boxed warning, but its label also requires liver tests before starting and one recheck at three months, and bars starting at the same twice-the-upper-limit threshold.
What to do
- Consider them when hormone therapy is ruled out or unwanted and hot flashes are disrupting your life.
- Get liver tests before the first dose; don't start if liver values are already twice the upper limit of normal.
- On fezolinetant, keep every follow-up liver test (months 1, 2, 3, 6 and 9); on elinzanetant, the one at three months.
- On fezolinetant, its label says to stop at once and get checked if signs of liver injury appear: new tiredness, poor appetite, nausea or vomiting, itching, yellowing skin or eyes, pale stools, dark urine or belly pain.
- If hot flashes mainly wreck your sleep, see insomnia treatment for how they fit alongside other options.
Further reading
- Lederman S et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 2023.[5]
- Pinkerton JV et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA 2024.[6]
- FDA drug safety communication — Veozah (fezolinetant) and serious liver injury. FDA, 2024.[7]